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- W2045014680 abstract "A validated LC–MS/MS method to determine the content of dipfluzine (Dip) and its three metabolites (M1, M2, and M5) simultaneously within rat plasma samples was developed. After a single liquid–liquid extraction, the assay was performed by using a C18 column and positive electrospray ionisation mode (ESI) in the multiple reaction monitoring (MRM) mode with transitions of m/z 417.3→167.3, 251.2→165.2, 199.1→121.3, and 183.2→105.1 for Dip, M1, M2, and M5, respectively. Sulfamethoxazole (SMZ) was used as internal standard (IS). The method was linear ranged from 0.5–518, 0.5–524, 1.0–1036, and 0.5–514 ng/ml for Dip, M1, M2, and M5, respectively and all correlation coefficients were greater than 0.9919. The intra- and inter-day precision values obtained were less than 11.5% and the accuracy was between −3.2 and 9.7% for each analyte. The extraction recoveries of their three concentrations for Dip and its three metabolites were all higher than 71.9%. The technique was successfully applied to a pharmacokinetic study of Dip and its metabolites after a single oral administration of Dip (20 mg/kg) to rats. The results indicated that the metabolite formation was rapid and generated M5 as the predominant metabolite, followed by M1 and M2. The maximum plasma concentrations (Cmax) were 59 ± 7, 37 ± 4, 3 ± 0.2, and 55 ± 5 ng/ml; the time to maximum plasma concentration (Tmax) were 65 ± 12, 95 ± 12, 190 ± 25, and 90 ± 0 min and the areas under the concentration–time curves (AUC0→∞) were 17573 ± 704, 8328 ± 355, 5602 ± 753, and 16101 ± 429 ng min/ml for Dip, M1, M2, and M5, respectively. These results suggested that Dip was extensively metabolized and rapidly absorbed. The half-life (t1/2) of Dip, M1, M2, and M5 were 329 ± 15, 767 ± 75, 2364 ± 434, and 378 ± 36 min, respectively, which indicated that Dip and M5 were eliminated quickly. M2 reached its Tmax later and exhibited a longer t1/2 than the other metabolites, which indicated that there might be some type of flip-flop mechanism at work in the pharmacokinetics of M2." @default.
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- W2045014680 date "2014-02-01" @default.
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- W2045014680 title "Pharmacokinetic evaluation of dipfluzine and its three metabolites in rat plasma using liquid chromatography–mass spectrometry" @default.
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- W2045014680 doi "https://doi.org/10.1016/j.jchromb.2013.12.018" @default.
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